热炎宁合剂的非临床幼年动物毒理学研究

目的:采用幼年动物对热炎宁合剂进行毒理学研究,进一步为其儿科用药提供临床前安全性数据。方法:采用10日龄SD大鼠连续36天灌胃给予热炎宁合剂,观察主要毒性靶器官及损害的可逆程度,评估大鼠产生的毒性反应及其严重程度。结果:给药后动物出现棕褐色水样便,与药物的药效作用相关;而深黄色尿液症状可能与受试物本身性状相关。离乳前高剂量组雌、雄动物体重下降,给药初期高剂量组雌、雄动物体重增长幅度减少;给药结束时高剂量组雌、雄动物血红蛋白、红细胞比容降低,雄性动物网织红细胞含量及比例升高;给药结束时高剂量组雌性动物血清中甘油三脂含量升高;给药组雌、雄性动物尿比重、尿酮体增加,尿颜色加深,雄性动物尿隐血含量增加、尿白细胞含量增加;以上指标在恢复期结束时均可恢复。此外,未观察到热炎宁合剂对其他指标的影响。给药组动物尿生化指标的变化并未观察到相应肾脏组织病理学的明显改变。结论:在本试验条件下,热炎宁合剂对幼龄动物不产生明显毒性作用的剂量为65.1 g/kg(相当于生药量)。这些结果为临床儿科剂量及毒副反应的监测提供参考依据。

Toxicological Studies of Reyanning Mixture on Juvenile Animals

Objective: To conduct toxicological research on Reyanning mixture using juvenile animals, and provide further preclinical safety data for its pediatric use. Methods: 10-day-old SD rats were intragastrically administrated with Reyanning mixture for 36 consecutive days, and the main toxic target organs and the reversibility of the damage, and to evaluate the toxicity and severity of the rats. Results: After the administration, the animals which appeared brown watery stools, was related to the drug effect; and the symptoms of dark yellow urine might be related to the properties of the test substance. The body weights of females and males in the high-dose group were decreased before weaning, and the weight gains of females and males in the high-dose group decreased at the initial stage of administration. The hemoglobin and hematocrit of the females and males in the high-dose group decreased at the end of the administration, and the number and proportion of reticulocytes of male animals in high-dose group increased. The serum triglyceride of the female animals in the high-dose group increased. In the administration groups, the urine specific gravity and urine ketone increased and the urine color darkened. The contents of urine occult blood and white blood cell in the male animals increased. All of the above indicators were restored at the end of the recovery period. In addition, no other abnormalities associated with the test article was found. No renal histopathological change, corresponding to the variations in the urine biochemical indexes, was observed. Conclusion: Under current experimental conditions, no observable adverse effect level of Reyanning Mixture on juvenile animals was 65.1 g/kg (equivalent to the amount of crude drug). These results provide a reference basis for the the clinical pediatirc dose design and toxic side effects monitoring.